Establishment of Analytical Methods for Quality Control of Live-Chimeric Dengue Vaccine

Abstract

The objective of this study was to establish the analytical methods for quality control of livechimeric dengue tetravalent vaccine, the first novel dengue vaccine in the world which could be submitted for marketing authorization according to manufacturer's specification and WHO's guidelines. The study steps included gap analysis for identification of method needed, laboratory preparedness, method verification or validation and establishment of standard method operating procedures. It was found that the method for identity, potency, stability in vero cell as well as water content by coulometric method were needed to be developed and validated/verified in our lab. The method validation of identity, potency and stability testing revealed that there were specificity against dengue serotype 1, 2, 3 and 4. The linearity showed coefficient of determination value (r') >0.996 whereas precision presented percent of coefficient of variation (%CV) ‹5 and accuracies were close to 100% for all serotypes. The method verification of water content presented CV <1 and < 10 for accuracy and precision respectively. Sterility test by membrane filtration and endotoxin content by LAL kinetic chromogenic confirmed suitability of the method and vaccine. Endotoxin test presented accuracy of recovery 89% and precision of %CV ‹3 at sample dilution of 1:100. It can be concluded that from these studies, all analytical methods for quality control of live-chimeric dengue vaccine were established according to manufacturer and international standards for consumer protection to access and obtain a qualified and safe vaccine.